U.K. Trial Launched to Deliberately Infect People with Covid after They Already Caught It

Researchers at the University of Oxford have launched a trial that will deliberately expose people who have already had Covid to the coronavirus again to study the level of immune protection needed to prevent reinfection. It is hoped that the study will aid the development of treatments and vaccines. The Guardian has the story.

The first human challenge trials for Covid began this year, with the study – a partnership led by researchers at Imperial College London among others – initially looking at the smallest amount of virus needed to cause infection among people who have not had Covid before.

Now researchers at the University of Oxford have announced that they have gained research ethics approval for a new human challenge trial involving people who have previously had coronavirus. Recruitment is expected to start in the next couple of weeks.

“The point of this study is to determine what kind of immune response prevents reinfection,” said Helen McShane, a Professor of Vaccinology at the University of Oxford, and Chief Investigator on the study.

McShane said the team would measure the levels of various components of participants’ immune response – including T-cells and antibodies – and then track whether participants became reinfected when exposed to the virus.

Participants must be healthy, at low risk from Covid, aged between 18 and 30, and must have been infected with the coronavirus at least three months before joining the trial. As well as having previously had a positive Covid PCR test, they must also have antibodies to Covid. Given the timing criteria, McShane said it was likely most participants would have previously been infected with the original strain of the virus.

The first phase of the trial will initially involve 24 participants split into dose groups of three to eight people who will receive, via the nose, the original strain of coronavirus. The idea is to start with a very low dose and, if necessary, increase the dose – up to a point – between groups…

The second phase of the study – expected to start in the summer – will involve a new group of participants and will study closely their immune response before and after exposure to the virus, as well as the level of virus and symptoms in those who become reinfected.

The vaccines which produce the required level of immunity – as determined by this study – could have their licensing fast-tracked without trials of thousands of people, according to Professor McShane.

If we can determine the level of immune response above which an individual cannot be infected, then that will help us determine whether new vaccines will be effective without necessarily having to test them in phase three efficacy trials.

Worth reading in full.

News Round Up

BMJ: 2020 Was Less Deadly Than Every Year Before 2009

Leading medical journal the BMJ published a peer-reviewed article last week by John Appleby, Director of Research at the Nuffield Trust, that draws on ONS data to look at the 2020 England and Wales death toll in a historical context.

In terms of absolute number of deaths, 2020 was the worst year since 1838 except for the Spanish Flu year of 1918 (note that overseas deaths including war casualties are not included).

Total deaths in England and Wales, 1838-2020

However, as a proportion of population, it was only the worst year since 2003.

Deaths per 100,000 population in England and Wales, 1838-2020

Furthermore, once you take into account the fact that the population is getting older and standardise the figures by age, 2020 was less deadly than 2008 and every year prior to it.

Age standardised mortality rates per 100,000 in England and Wales, 1942-2020

Appleby for his part makes no attempt to downplay the pandemic death toll, pointing out that only in four previous years had there been a sharper increase in percentage terms on the previous year and they were all prior to 1941. It was definitely counter to the decreasing trend.

A point he doesn’t make, however, is that the historically low levels of the previous 11 years would have left an unusually large amount of ‘dry tinder’ for any novel virus to burn through. Plus, 2019 had the lowest age-standardised mortality ever, to the extent that if you took an average of 2019 and 2020 then that average was lower than 2015, 2013, 2012 and every year prior to 2011. While it’s fair to note (as Appleby does) that the coronavirus epidemic continued into 2021, with high excess deaths in January and February, it is hard to regard this as an earth-shattering death toll.

The graphs also make clear that previous similar pandemics, such as in 1957 and 1968, made only a modest impact on mortality and only for a year or two, notwithstanding the lack of vaccines or social interventions. There is nothing about this disease to think the long-term pattern should be any different that would justify some kind of radical, permanent change to the way we interact or organise our lives. It’s important to remember that our immune systems develop and maintain resistance to a host of pathogens through being frequently exposed to them and that social isolation, where it is not merely ineffective, can deprive us of the opportunity to keep our immunity topped up.

The BMJ article is worth reading in full.

Israel Begins to Ease Lockdown Restrictions as around 80% Of Its Population Are Now Vaccinated

With almost 80% of its population having been vaccinated, Israel has scrapped the requirement for people to wear face masks outdoors. The rule has been in place – for all outdoor activities not relating to exercise – for the past year. The Mail has the story.

Israel has dropped its almost year-long outdoor mask mandate as it inches towards total immunisation of its adult population. 

The restriction, which required masks to be worn outdoors unless exercising, was lifted on Sunday as Reuters reported that the country had vaccinated around 80% of its adult population. 

“The rate of infection in Israel is very low thanks to the successful vaccine campaign in Israel, and therefore it is possible to ease [restrictions],” Health Minister Yuli Edelstein said on Thursday, adding that masks will still be required indoors.

Israel’s highly successful vaccination campaign has seen close to five million of its 9.3 million people vaccinated, according to Reuters.

The drive has drastically cut hospitalisations and deaths from coronavirus. 

Israeli Prime Minister Benjamin Netanyahu obtained millions of Pfizer/BioNTech vaccines in part by agreeing to share with Pfizer medical data on the product’s impact.

The vaccines have transformed life in Israel. In mid-January the country had a peak of some 10,000 new infections a day but the rate is now about 200 cases a day.

The rate of new infections has remained low even after in-person learning resumed and restrictions were loosened on bars, restaurants and indoor gatherings.

Strict measures also remain in place for anyone entering the country with citizens and foreigners alike required to self isolate.   

“We are leading the world right now when it comes to emerging from the coronavirus,” Prime Minister Benjamin Netanyahu told reporters. “(But) we have still not finished with the coronavirus. It can return.”  

Pfizer CEO Albert Bourla was a guest of honour at a Government ceremony on Wednesday evening marking the 73rd anniversary of the founding of Israel…

Throughout the festivities marking the anniversary, thousands of people held barbecues, lounged on beaches and celebrated at parties, often without masks.

“Breathing Freely,” read the cover headline of the mass-circulation daily Israel Hayom, as reported by Reuters.

The Mail’s report is worth reading in full.

Deaths Linked to Covid Vaccines are 30 Times More Common than with Other Vaccines – Is the Safety Reporting System Fit for Purpose?

There follows a guest post by Dr Ros Jones, a retired Consultant Paediatrician and member of HART.

We have heard a lot in the last few weeks about Yellow Card reports for any adverse effects of vaccination, so I shall seek here to give a little background to the system and where it can work well but where it can seriously fall short. 

The Yellow Card system was introduced in 1964 following the thalidomide disaster as a way of formalising the reporting of adverse effects, especially for new drugs. Tear-out cards, printed on yellow paper, were inserted at the back of the British National Formulary (BNF), which acts as the bible for UK prescribing. This book, updated twice yearly, was given to every practising doctor. Any doctor or pharmacist seeing a patient with unexpected symptoms relating to a prescribed medicine could quickly complete one of the cards and send it to the regulatory authority. But already you can spot the problem here – the system depends on the health care professional recognising that the symptom might be related to a particular drug, so if the connection is not made then neither is the report. Take for example a busy orthopaedic SHO treating an elderly lady with a fractured hip. Will they think to report this as an adverse reaction to her blood pressure tablets? This matters. Studies show up to one third of hospital admissions are due to iatrogenic causes i.e., drug side-effects. Nowadays, the BNF is an online book and the Yellow Card system is also online, so perhaps even more ‘out of sight, out of mind’, especially if the ward is really busy at the time. If you ask colleagues whether vaccine adverse outcomes have been reported to MHRA, they often reply: “I’m not convinced it was the cause, it could have been due to anything.” But physicians are not responsible for deciding whether a clinical event was caused by a drug or was coincidental – that is the role of the MHRA

All new drugs and vaccines are subject to trials, starting with animal trials usually involving a number of different species, then building gradually through small pilot studies on humans to establish dosage regimes (for example) and short term safety, before rolling out to large scale trials looking for both efficacy and longer term safety. In such trials, all adverse outcomes will be reported, with the control group acting as the base-line for any symptoms against which the new drug is compared. The system works well for reasonably common side-effects and here the size of the trials is important. You will see in drug information leaflets side effects listed as “very common: affecting greater than 1 in 10 people”, through to “very rare: affecting less than 1 in 10,000”. Generally speaking, “very rare” side effects are only listed if severe. Many drug and vaccine trials are only large enough to detect “uncommon” side effects and for any new drug it is only through post-marketing surveillance that rarer side-effects can be discovered. New drugs are marked in the BNF with a black triangle for two years, to remind doctors to complete yellow card reports. In addition, most drug trials will exclude certain groups – for example children, pregnant women and people with risk factors such as kidney and liver disease, so safety for these groups is very much dependent on animal studies or assumptions from other similar drugs. Species difference in adverse effects may occur too, so damage to the developing foetus may only be seen after a drug starts being used by humans. Certain age groups that are under-represented in trials, such as the very elderly, may also be at greater risk. If post-marketing surveillance reveals an unexpected problem then the drug licence may be withdrawn or modified (e.g. limited to certain age groups, as with the AstraZeneca vaccine). 

Toby Green’s New Book is the Perfect Cure For the Covid Lobotomy

We’re publishing a short piece today by Lockdown Sceptics regular Sinéad Murphy, a Research Associate in Philosophy at Newcastle University, in which she praises a new book by Toby Green. Called The Covid Consensus: The New Politics of Global Inequality, it’s an exploration of why the lockdown policy has commanded such support from people on the left and right of politics, in spite of its catastrophic consequences. In particularly, why has the left been so enthusiastic about lockdowns when it was obvious from the beginning that the world’s poorest people would suffer the most as a result of the policy? Dr Murphy thinks this book is the perfect cure for those who’ve been lobotomised by pro-lockdown propaganda.

We might think that the time is passing for this book; we are on the way out of lockdown, after all. But Boris Johnson’s murmurings last Monday, that the reduction in cases and deaths in the UK since the end of January is due, not to the injections but to the lockdown, surely signal that the likelihood of another lockdown is very high. And we ought not to forget that the conditions of our lives at this moment, even in the midst of the easing, continue to be more restrictive than any in history.

In fact, The Covid Consensus could not be more timely. Its coming out only shortly over a year after the onset of societal and personal conditions deeply erosive of energy and purpose is worthy of our grateful acknowledgment.

Sinéad’s piece is worth reading in full.

Incidentally, Toby Green is a senior lecturer in Lusophone African history and culture at King’s College London and is author of The Rise of the Trans-Atlantic Slave Trade in Western Africa, 1300–1589. We will be publishing a piece by him about his new book shortly.

International Travel Restrictions Likely to Be In Place For Some Time, Says Nicola Sturgeon

Concerns over new Covid variants continue to hamper the narrative regarding Britain’s unlock. Nicola Sturgeon has warned that restrictions on international travel should not be lifted too soon because of the “big risk” of importing Covid variants into the UK. Scotland’s First Minister also told Sophy Ridge on Sky News that the British Government’s “traffic light” system for international travel is not fit for purpose because “we don’t know where the next dangerous variant will come from“.

The Daily Record has the story.

Nicola Sturgeon has warned Scotland faces a “big risk” of importing new variants of the coronavirus if restrictions on international travel are lifted too soon.

The First Minister admitted lifting travel abroad “too quickly” last year which allowed the virus to re-seed amongst the population, which then lead to a second national lockdown.

Speaking on the Sophy Ridge on Sunday show, the SNP leader said Scots face living longer with international travel restrictions due to the risk of importing new strains of Covid. 

She added: “The big risk that we face, not just in Scotland but in the UK, is the importation of new variants of the virus.

“Variants that might be faster spreading, that might be more severe, and crucially variants that might undermine the efficacy of the vaccines.

“We have to be very careful about that which is why I think one of the restrictions we’re all going to have to live with for longer is a restriction on international travel.

“We must not allow the progress we are making domestically to be undermined by a too lax position on international travel.”

… Asked about the fast-spreading Indian variant, Sturgeon said: … “It is a variant of interest as oppose to a variant of concern.”

Worth reading in full.

SAGE Modelling From May Last Year Said Approach Recommended in Great Barrington Declaration Was Least Bad Alternative to Lockdown

We’re publishing an original piece today by Lockdown Sceptics regular Glen Bishop, a second year maths student at Nottingham University. Glen has read a paper released by the Warwick modelling team that is part of SAGE’s SPI-M group last May and uncovered some interesting facts. Not the least of these is that when the team modelled what the signatories of the Great Barrington Declaration refer to as “Focused Protection”, i.e. protecting the elderly and allowing those who aren’t vulnerable to the disease to go about their lives taking sensible precautions, as they would during a normal flu season, the projected loss of life between March 2020 and May 2021 was 138,000, only 11,000 more than the 127,000 that have supposedly died from Covid already, with the Government embracing the suppression strategy endorsed by SPI-M. The modelling team also acknowledges that of all the alternatives to an indiscriminate lockdown, shielding those aged 60 and over would have resulted in the least loss of life as well as the least socio-economic disruption. Here’s the key paragraph from the Warwick paper:

A completely uncontrolled outbreak is predicted to lead to around 200,000 deaths, approximately 2 million QALY losses but no lockdown impacts. If the current controls are maintained until the end of 2020, then we predict 39,000 deaths this year [2020], but a further 159,000 if controls were then completely removed. Regional switching and age-dependent strategies provide alternative exit strategies in the absence of pharmaceutical interventions. Of these, the age-dependent shielding of those age 60 or over generates the lowest mortality and also the lowest lockdown scale, thereby minimising socio-economic disruption. However, it is unclear if a protracted lockdown of this age-group would be practical, ethical or politically acceptable.

Glen’s article is worth reading in full.

Too Early to Tell If Hospitality Can Reopen On May 17th, Says Minister

It is still “too early to say” whether the reopening of indoor hospitality can take place on May 17th, according to the Environment Minister. George Eustice told Andrew Marr on the BBC that while Britain’s vaccine rollout is “on track” (with 10 million second doses expected to have been administered by the end of the weekend), the risk of Covid variants could delay the next step in the Government’s “roadmap” out of lockdown. He is quoted on the Guardian website:

Well, it is too early to say. But I think we are on track in the sense that we are on track with the rollout of the vaccination programme. We have now vaccinated everybody over the age of 50 and this week they are offering vaccinations as well to those under the age of 50, starting with the 45-to-59 year-olds – so that bit is on track.

But we are being a bit cautious here. So although we have now got 60% of the adult population vaccinated we do just have to keep a close eye on these variants of concern.

Also, see what the impacts are of the easements we have just made, the loosenings we have just made, before moving to the next stage.

He delivered a similar message to Sophy Ridge on Sky News:

The biggest threat to everything we’re doing at the moment is that at some point there will be a variant that manages to evade the vaccine or largely evade it, so it is high on our concerns which is why while the vaccine rollout has been incredibly successful with over 60% of the adult population now vaccinated, we continue to proceed with some caution as we come out of lockdown.

The impact of the partial easing of lockdown earlier this month has been tempered by the weather (of course!) and by the fact that a “large proportion” of hospitality businesses do not have access to sufficient outdoor space. Kate Nicholls, the Chief Executive of UK Hospitality, said that even those venues which were able to reopen outdoors “still aren’t going to break even… the best they are going to achieve outdoors is 20%”, highlighting the need to allow businesses to open fully – that is, indoors.

Imperial College’s Danny Altmann said on Friday that “we should be terribly concerned” about the emergence of the Indian Covid variant in Britain, which could “scupper” the “roadmap” out of lockdown – a statement which a member of the Joint Committee on Vaccination and Immunisation (JCVI) says is “pessimistic“. The Evening Standard reported:

Imported coronavirus variants are unlikely to set lockdown easing back to “square one” because immunity from vaccines “won’t just disappear”, according to a key figure on the UK’s immunisation committee.

Professor Adam Finn, a member of the JCVI, said he expected a “gradual erosion” of vaccine protection as the virus evolves but not enough to “scupper” the Prime Minister’s roadmap, as one leading scientist had predicted.

Meanwhile, Covid cases have fallen to a seven-month low in England.

Britain’s Regulator Missed Early Blood Clot Cases Linked to AstraZeneca Vaccine

By the time cases of blood clotting in patients who had received the AstraZeneca vaccine had begun to emerge on the Continent (in March), Britain had already administered 11 million doses (the first ones having been given in January). No such adverse events had been reported publicly in Britain, but not for a lack of cases, according to the findings of a new investigation. Clotting cases were recorded in the UK’s Yellow Card database (a website for reporting adverse drug reactions) in January but were missed at first by the Medicines and Healthcare products Regulatory Agency (MHRA) – possibly due to the algorithms it uses to interrogate UK data. The Telegraph has the story.

On March 11th, the MHRA put out a statement saying it could see no evidence of a problem…

But the MHRA was, it appears, wrong. An investigation by the Telegraph has established that signals had been firing unnoticed in the UK’s Yellow Card database for at least a month, perhaps longer.

In January, a patient suffered a brain clot following their first dose of the AstraZeneca jab… Then in early February, two similar cases followed, including a death and a life-changing CVST clot in a young adult. All had low platelets and all were reported into the Yellow Card system.

On Friday, the MHRA told the Telegraph: “We are aware of thromboembolic events that occurred in January, however, our first report was received in the week commencing February 8th…. we cannot disclose information about individual cases to protect patient and reporter confidentiality.”

… The MHRA faces serious questions as to why it did not detect the signals sooner. The issue is not that it has been left looking flatfooted or even that earlier detection would necessarily have altered its advice, but that the delay left it unable to shape international policy and confidence in what remains a vital vaccine in the fight against Covid for the world.

Professor Stephan Lewandowsky, a psychologist at the University of Bristol studying the rollout of Covid vaccines, told the Financial Times on Friday: “The MHRA was slow in responding to the emergence of a specific constellation of symptoms associated with the AstraZeneca vaccine and slow to communicate what they were finding – and I am not the only one who thinks so.”

This slow repose was caused, it is said, by algorithms which were not as sensitive as the ones used by European health agencies to sift through data.

From January 4th to March 14th, a total of 532 “blood system events”, including 20 deaths, came through the UK’s Yellow Card system relating to the AstraZeneca jab, according to an analysis of published MHRA data by Dr Hamid Merchant, a pharmaceutical scientist at the University of Huddersfield. There were thousands of non-blood-related reports besides.

Of the thrombotic events recorded, four related to CVST (but no deaths were recorded), 55 were non-site specific and there were clusters of 64 and 66 cases in the lungs and deep veins respectively. There were then 267 general bleeding events and six deaths, three of which resulted from cerebral haemorrhage. Finally, there were 60 cases of thrombocytopenia, including two deaths.

To sift such data, regulators build algorithms that must balance “sensitivity” against leg-work. The more sensitive the algorithm, the more warning signals it will throw up to investigate – and many of those labour-intensive investigations will prove fruitless.

It is not known exactly what parameters the MHRA set but it is clear they were not as sensitive as those used by some regulators in Europe.